奥沙利铂对人结肠癌细胞LoVo和SW480/M5作用的实验研究

目的探讨体外实验奥沙利铂对人结肠癌LoVo和SW480/M5细胞的抑制作用及其可能机制。方法 MTT法检测不同剂量奥沙利铂对LoVo和SW480/M5细胞增殖的抑制作用。流式细胞仪检测1/2GI₅₀和GI₅₀浓度奥沙利铂对LoVo和SW480/M5细胞周期和早期凋亡的影响。原子光谱吸收仪检测GI₅₀浓度奥沙利铂作用4、8、24h后LoVo和SW480/M5细胞DNA含铂量。结果奥沙利铂对LoVo和SW480/M5细胞增殖的抑制作用呈量效依赖;其GI₅₀浓度:LoVo细胞为6.5mg/L,SW480/M5细胞为58.0mg/L。自然对数增殖周期,LoVo细胞中G₁期细胞比例高于、G₂期细胞比例低于SW480/M5细胞（P<0.05）。奥沙利铂浓度GI₅₀时,降低肿瘤细胞G₁期比例,升高LoVo细胞S期比例较SW480/M5细胞明显,升高SW480/M5细胞而降低LoVo细胞G₂/M期比例。1/2GI₅₀、GI₅₀奥沙利铂均可诱导两种肿瘤细胞发生早期凋亡,但1/2GI₅₀L-OHP促凋亡作用两种肿瘤细胞间无统计学差异,GI₅₀L-OHP对LoVo细胞的促凋亡作用高于SW480/M5细胞。GI₅₀L-OHP奥沙利铂使两种肿瘤细胞DNA含铂量显著升高,并呈时效依赖。LoVo细胞DNA交联铂原子能力高于SW480/M5细胞。结论奥沙利铂主要通过阻滞细胞于S期或（和）G₂/M期并诱导细胞凋亡而抑制两种肿瘤细胞增殖。LoVo细胞对奥沙利铂敏感性明显高于SW480/M5细胞。

Effect of oxalioplatin on human colorectal cancer cell line LoVo and cell subline SW480 / M5

Objective To investigate the inhibitory effect of oxalioplatin （L-OHP） on human colorectal cancer cell line LoVo and cell subline SW480 / M5 , and its possible mechanisms. Methods The inhibitory effect of L-OHP at different doses on LoVo and SW480 / M5 cells was determined by MTT assay. Cell cycle and cell apoptosis of both cell lines that were wild or treated with L-OHP at 1 / 2GI₅₀ and GI₅₀ concentrations were determined by flow cytometry. The Pt-DNA adducts of both cell lines treated with L-OHP at GI₅₀ dose for different times were detected by atomic absorption spectrometry. Results L-OHP inhibited proliferation of both LoVo and SW480 / M5 cell lines in a dose-dependent manner. The GI₅₀ of LoVo cells was 6.5 mg / L, while that of SW480 / M5 cells was 58.0 mg / L. In wild types , the percentage of G₁ -phase cells was significantly higher , and that of G₂ -phase cells was lower in LoVo cells than those in SW480 / M5 cells. GI₅₀ L-OHP decreased the percentage of G₁ -phase cells, increased the percentage of S-phase cells, significantly more in LoVo cells than those in SW480 / M5 cells. GI₅₀ L-OHP decreased the percentage of G₂ -phase cells in LoVo cells, but decreased that in SW480 / M5 cells. L-OHP at 1 / 2 GI₅₀ or GI₅₀ concentration induced apoptosis of both cell lines. There was no significant difference inimprovement of apoptosis induced by 1 / 2 GI₅₀ L-OHP, but significant difference in such improvement of apoptosis induced by GI₅₀ L-OHP, between the two cell lines. GI₅₀ L-OHP increased the levels of Pt-DNA adducts in both cell lines in a time-dependent manner. The capacity of Pt-DNA adducting in LoVo cells was significantly higher than that in SW480 / M5 cells. Conclusions L-OHP can inhibit the growth of both L-OHP and SW480 / M5 cells by blocking the cells into S-phase or （and G₂ -phase） and inducing apoptosis. LoVo cells are more sensitive to L-OHP than SW480 / M5 cells.